音猬因子是否参与人类骨折愈合？——一项关于音猬因子局部和全身浓度的前瞻性研究。

Is sonic Hedgehog involved in human fracture healing? --a prospective study on local and systemic concentrations of SHH.

作者信息

Eipeldauer Stefan, Thomas Anita, Hoechtl-Lee Leonard, Kecht Mathias, Binder Harald, Koettstorfer Julia, Gregori Markus, Sarahrudi Kambiz

机构信息

University Clinic for Traumatology, Medical University of Vienna, Vienna, Austria.

Department of Gender Medicine, Medical University of Vienna, Vienna, Austria.

出版信息

PLoS One. 2014 Dec 11;9(12):e114668. doi: 10.1371/journal.pone.0114668. eCollection 2014.

DOI:10.1371/journal.pone.0114668

PMID:25501422

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4263617/

Abstract

INTRODUCTION

Sonic Hedgehog (SHH) is a new signalling pathway in bone repair. Evidence exist that SHH pathway plays a significant role in vasculogenesis and limb development during embryogenesis. Some in vitro and animal studies has already proven its potential for bone regeneration. However, no data on the role of SHH in the human fracture healing have been published so far.

METHODS

Seventy-five patients with long bone fractures were included into the study and divided in 2 groups. First group contained 69 patients with normal fracture healing. Four patients with impaired fracture healing formed the second group. 34 volunteers donated blood samples as control. Serum samples were collected over a period of 1 year following a standardized time schedule. In addition, SHH levels were measured in fracture haematoma and serum of 16 patients with bone fractures.

RESULTS

Fracture haematoma and patients serum both contained lower SHH concentrations compared to control serum. The comparison between the patients' serum SHH level and the control serum revealed lower levels for the patients at all measurement time points. Significantly lower concentrations were observed at weeks 1 and 2 after fracture. SHH levels were slightly decreased in patients with impaired fracture healing without statistical significance.

CONCLUSION

This is the first study to report local and systemic concentration of SHH in human fracture healing and SHH serum levels in healthy adults. A significant reduction of the SHH levels during the inflammatory phase of fracture healing was found. SHH concentrations in fracture haematoma and serum were lower than the concentration in control serum for the rest of the healing period. Our findings indicate that there is no relevant involvement of SHH in human fracture healing. Fracture repair process seem to reduce the SHH level in human. Further studies are definitely needed to clarify the underlying mechanisms.

摘要

引言

音猬因子（SHH）是骨修复中的一条新信号通路。有证据表明，SHH通路在胚胎发育过程中的血管生成和肢体发育中起重要作用。一些体外和动物研究已经证明了其在骨再生方面的潜力。然而，迄今为止尚未发表关于SHH在人类骨折愈合中作用的数据。

方法

75例长骨骨折患者纳入本研究并分为两组。第一组包含69例骨折愈合正常的患者。4例骨折愈合受损的患者组成第二组。34名志愿者捐献血样作为对照。按照标准化时间表在1年时间内收集血清样本。此外，还测量了16例骨折患者骨折血肿和血清中的SHH水平。

结果

与对照血清相比，骨折血肿和患者血清中的SHH浓度均较低。患者血清SHH水平与对照血清的比较显示，在所有测量时间点患者的SHH水平均较低。骨折后第1周和第2周观察到浓度显著降低。骨折愈合受损患者的SHH水平略有下降，但无统计学意义。

结论

这是第一项报告人类骨折愈合中SHH局部和全身浓度以及健康成年人SHH血清水平的研究。发现在骨折愈合的炎症期SHH水平显著降低。在愈合期的其余时间，骨折血肿和血清中的SHH浓度低于对照血清中的浓度。我们的研究结果表明，SHH与人类骨折愈合无关。骨折修复过程似乎会降低人体内的SHH水平。肯定需要进一步研究来阐明其潜在机制。